The authors respond to "Concerns about subgroup analyses and reason for stopping remdesivir trial".
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ABSTRACT:
SUBMITTER: Murthy S
PROVIDER: S-EPMC8920528 | biostudies-literature | 2022 Mar
REPOSITORIES: biostudies-literature
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The authors respond to "Concerns about subgroup analyses and reason for stopping remdesivir trial".
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20220301 10
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Project description: Not available
| S-EPMC10563862 | biostudies-literature
Project description:BackgroundTraditional approaches to subgroup analyses that test each moderating factor as a separate hypothesis can lead to erroneous conclusions due to the problems of multiple comparisons, model misspecification, and multicollinearity.ObjectiveTo demonstrate a novel, systematic approach to subgroup analyses that avoids these pitfalls.MethodsA Best Approximating Model (BAM) approach that identifies multiple moderators and estimates their simultaneous impact on treatment effect sizes was applied to a randomized, controlled, 11-week, double-blind efficacy trial on smoking cessation of adult smokers with attention-deficit/hyperactivity disorder (ADHD), randomized to either OROS-methylphenidate (n = 127) or placebo (n = 128), and treated with nicotine patch. Binary outcomes measures were prolonged smoking abstinence and point prevalence smoking abstinence.ResultsAlthough the original clinical trial data analysis showed no treatment effect on smoking cessation, the BAM analysis showed significant subgroup effects for the primary outcome of prolonged smoking abstinence: (1) lifetime history of substance use disorders (adjusted odds ratio [AOR] 0.27; 95% confidence interval [CI] 0.10-0.74), and (2) more severe ADHD symptoms (baseline score >36; AOR 2.64; 95% CI 1.17-5.96). A significant subgroup effect was also shown for the secondary outcome of point prevalence smoking abstinence--age 18 to 29 years (AOR 0.23; 95% CI 0.07-0.76).ConclusionsThe BAM analysis resulted in different conclusions about subgroup effects compared to a hypothesis-driven approach. By examining moderator independence and avoiding multiple testing, BAMs have the potential to better identify and explain how treatment effects vary across subgroups in heterogeneous patient populations, thus providing better guidance to more effectively match individual patients with specific treatments.
| S-EPMC4817346 | biostudies-literature
Project description:ObjectivesTo systematically review reports that queried abstract authors about reasons for not subsequently publishing abstract results as full-length articles.Study design and settingSystematic review of MEDLINE, EMBASE, The Cochrane Library, ISI Web of Science, and study bibliographies for empirical studies in which investigators examined subsequent full publication of results presented at a biomedical conference and reasons for nonpublication.ResultsThe mean full publication rate was 55.9% [95% confidence interval (CI): 54.8%, 56.9%] for 24 of 27 eligible reports providing this information and 73.0% (95% CI: 71.2%, 74.7%) for seven reports of abstracts describing clinical trials. Twenty-four studies itemized 1,831 reasons for nonpublication, and six itemized 428 reasons considered the most important reason. "Lack of time" was the most frequently reported reason [weighted average = 30.2% (95% CI: 27.9%, 32.4%)] and the most important reason [weighted average = 38.4% (95% CI: 33.7%, 43.2%)]. Other commonly stated reasons were "lack of time and/or resources," "publication not an aim," "low priority," "incomplete study," and "trouble with co-authors."ConclusionsAcross medical specialties, the main reasons for not subsequently publishing an abstract in full lie with factors related to the abstract author rather than with journals.
| S-EPMC4458220 | biostudies-literature
Project description: Not available
| S-EPMC7012631 | biostudies-literature
Project description:Background and purposeMore than 50% of patients with acute intracerebral hemorrhage (ICH) are taking antihypertensive drugs before ictus. Although antihypertensive therapy should be given long term for secondary prevention, whether to continue or stop such treatment during the acute phase of ICH remains unclear, a question that was addressed in the Efficacy of Nitric Oxide in Stroke (ENOS) trial.MethodsENOS was an international multicenter, prospective, randomized, blinded endpoint trial. Among 629 patients with ICH and systolic blood pressure between 140 and 220 mmHg, 246 patients who were taking antihypertensive drugs were assigned to continue (n = 119) or to stop (n = 127) taking drugs temporarily for 7 days. The primary outcome was the modified Rankin Score at 90 days. Secondary outcomes included death, length of stay in hospital, discharge destination, activities of daily living, mood, cognition, and quality of life.ResultsBlood pressure level (baseline 171/92 mmHg) fell in both groups but was significantly lower at 7 days in those patients assigned to continue antihypertensive drugs (difference 9.4/3.5 mmHg, P < .01). At 90 days, the primary outcome did not differ between the groups; the adjusted common odds ratio (OR) for worse outcome with continue versus stop drugs was .92 (95% confidence interval, .45-1.89; P = .83). There was no difference between the treatment groups for any secondary outcome measure, or rates of death or serious adverse events.ConclusionsAmong patients with acute ICH, immediate continuation of antihypertensive drugs during the first week did not reduce death or major disability in comparison to stopping treatment temporarily.
| S-EPMC4851456 | biostudies-literature
Project description:BackgroundIt has been argued that postoperative pain treatment should be "procedure-specific", since different analgesics may have specific effects dependent on the surgical procedure. The aim of the present subgroup analysis was to compare the beneficial and harmful effects of perioperative gabapentin treatment in different surgical procedures.MethodsRelevant databases were searched for randomized clinical trials (RCTs) comparing gabapentin versus placebo. Two authors independently screened titles and abstracts, extracted data and assessed risk of bias. The primary outcomes were differences in 24-h morphine consumption, and serious adverse events (SAE) between surgical procedures. These subgroup analyses were predefined in a PRISMA compliant systematic review registered at PROSPERO (ID: CRD42013006538). It was predefined that conclusions should primarily be based on trials classified as overall low risk of bias.ResultsSeventy-four RCTs with 5645 patients were included, assessing benefit and harm in cholecystectomy, hysterectomy, mastectomy, and arthroplasty surgery, spinal surgery, and thoracic surgery. Only eight of 74 trials were classified as overall low risk of bias limiting our ability to conclude on the estimates in most meta-analyses. The differences between surgical procedures in these trials were not statistically significant when tested for subgroup differences. Fifteen trials with 1377 patients reported a total of 59 SAEs, most of which were observed in the thoracic surgery group.ConclusionBoth beneficial and harmful effects in these subgroup analyses were influenced by bias and insufficient data, limiting conclusions. With these limitations, we could not adequately test for differences in beneficial or harmful outcomes between six surgical subgroups undergoing perioperative gabapentin treatment.
| S-EPMC5480107 | biostudies-literature
Project description:BackgroundRemdesivir is approved for treatment of coronavirus disease 2019 (COVID-19) in nonhospitalized and hospitalized adult and pediatric patients. Here we present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resistance analyses from the phase 3 ACTT-1 randomized placebo-controlled trial conducted in adult participants hospitalized with COVID-19.MethodsSwab samples were collected at baseline and longitudinally through day 29. SARS-CoV-2 genomes were sequenced using next-generation sequencing. Phenotypic analysis was conducted directly on participant virus isolates and/or using SARS-CoV-2 subgenomic replicons expressing mutations identified in the Nsp12 target gene.ResultsAmong participants with both baseline and postbaseline sequencing data, emergent Nsp12 substitutions were observed in 12 of 31 (38.7%) and 12 of 30 (40.0%) participants in the remdesivir and placebo arms, respectively. No emergent Nsp12 substitutions in the remdesivir arm were observed in more than 1 participant. Phenotyping showed low to no change in susceptibility to remdesivir relative to wild-type Nsp12 reference for the substitutions tested: A16V (0.8-fold change in EC50), P323L + V792I (2.2-fold), C799F (2.5-fold), K59N (1.0-fold), and K59N + V792I (3.4-fold).ConclusionsThe similar rate of emerging Nsp12 substitutions in the remdesivir and placebo arms and the minimal change in remdesivir susceptibility among tested substitutions support a high barrier to remdesivir resistance development in COVID-19 patients. Clinical Trials Registration. NCT04280705.
| S-EPMC10629708 | biostudies-literature
Project description:Title: Gene Expression in Ara-C Resistance in AML A microarray study of altered gene expression in acute myeloid leukemia cell lines Keywords: cell type comparison Keywords: Expression profiling by array
2005-09-01 | GSE2788 | GEO
Project description:BackgroundInternet is a particularly dynamic way to quickly capture the perceptions of a population in real time. Complementary to traditional face-to-face communication, online social networks help patients to improve self-esteem and self-help.ObjectiveThe aim of this study was to use text mining on material from an online forum exploring patients' concerns about treatment (antidepressants and anxiolytics).MethodsConcerns about treatment were collected from discussion titles in patients' online community related to antidepressants and anxiolytics. To examine the content of these titles automatically, we used text mining methods, such as word frequency in a document-term matrix and co-occurrence of words using a network analysis. It was thus possible to identify topics discussed on the forum.ResultsThe forum included 2415 discussions on antidepressants and anxiolytics over a period of 3 years. After a preprocessing step, the text mining algorithm identified the 99 most frequently occurring words in titles, among which were escitalopram, withdrawal, antidepressant, venlafaxine, paroxetine, and effect. Patients' concerns were related to antidepressant withdrawal, the need to share experience about symptoms, effects, and questions on weight gain with some drugs.ConclusionsPatients' expression on the Internet is a potential additional resource in addressing patients' concerns about treatment. Patient profiles are close to that of patients treated in psychiatry.
| S-EPMC5673886 | biostudies-literature
Project description:ObjectiveTo investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications.DesignCohort of protocols of randomised controlled trial and subsequent full journal publications.SettingSix research ethics committees in Switzerland, Germany, and Canada.Data sources894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications.ResultsOf 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis.ConclusionsSubgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials.
| S-EPMC4100616 | biostudies-literature